Compelling evidence now associates specific human papillomavirus types (HPVs) with certain human anogenital cancers, most notably cervical carcinoma. Of the over 60 different HPVs now described, approximately 20 are associated with anogenital lesions. These genital tract HPVs can be further classified as either "high risk" or "low risk" by virtue of their association with lesions that have a risk for malignant progression. The "low risk" HPVs, such as HPV-6 and HPV-11, are associated with anogenital warts that rarely progress to malignancy. In contrast, the "high risk" viruses, such as HPV-16 and HPV-18, are associated with cervical intraepithelial neoplasia which are at risk for malignancy. A variety of studies have indicated that the "high risk" HPVs contain two genes (E6 and E7) which have transforming properties. The HPV-16 E7 protein is a multifunctional protein with transcriptional modulatory and transforming properties similar to the adenovirus (Ad) E1A proteins. The N-terminal 37 amino acids encoded by the anogenital associated HPVs are highly conserved and are similar to portions of the Ad E1A conserved regions 1 and 2 involved in complexing a number of host cellular proteins, including the retinoblastoma susceptibility gene product (pRB). The E7 protein can also bind pRB and the "high risk" HPV-16 and HPV-18 derived E7 proteins have a higher affinity for this binding than the E7 proteins encoded by the "low risk" HPV-6 and HPV-11. The biologic properties have been mapped to specific regions of the E7 protein and studies with chimeric HPV-6/HPV-16 E7 proteins have revealed differences in the biological and biochemical properties of E7 proteins derived from "high risk" HPVs and "low risk" HPVs.